Binding of (3H) kainic acid ((3H)KA) to neural sites was studied in invertebrates and vertebrates. Maximal binding is noted in brains of the frog, spiny dogfish, goldfish and chick. Significant binding is observed in some of the lowest forms. Generally, binding is to both high (KD equals 3-14nM) and low (KD equals 25-50nM) affinity receptors. In non-mammalian chordates, binding occurs in the cerebellum, with less in forebrain and least in the medulla. In mammals, maximal binding occurs in forebrain, with less in the cerebellum, and least in the medulla. Frog brain, rat forebrain and human parietal cortex show similar binding kinetics. In these vertebrates, unlabeled kainic acid (KA) is the most potent inhibitor of (3H) KA binding. Reduction of the isopropylene side chain of KA reduces potency. L-glutamate is less potent than KA; D-glutamate is less potent than L-glutamate. The widespread distribution of highly specific (3H)KA binding sites in neural tissue and the similar binding characteristics of these sites in divergent vertebrate species suggest the presence of an endogenous neuronal system that has not changed appreciably through evolution.